Diagnostic criteria for apathy in neurocognitive disorders

Miller, David S.; Robert, Philippe; Ereshefsky, Larry; Adler, Lawrence; Bateman, Daniel R.; Cummings, James M.; DeKosky, Steven T.; Fischer, Corinne E.; Husain, Masud; Ismail, Zahinoor; Jaeger, Judith; Lerner, Alan J.; Li, Abby; Lyketsos, Constantine G.; Manera, Valéria; Mintzer, Jacobo; Moebius, Hans J; Mortby, Moyra E.; Meulien, Didier; Pollentier, Stephane; Porsteinsson, Anton P.; Rasmussen, J.; Rosenberg, Paul B.; Ruthirakuhan, Myuri; Sano, Mary; Sarracini, Carla Zucchero; Lanctôt, Krista L.

doi:10.1002/alz.12358

Cited by 96 publications

(89 citation statements)

References 137 publications

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“…However, update diagnostic criteria have sought to rectify such confusion. 4,37 While apathy is common in dementia and has been linked to poorer prognosis, 67 its assessment is challenging. Discrepancies in reported prevalence estimates and frequencies have been attributed to a lack of standardized diagnostic criteria and assessment methods.…”

Section: Assessmentmentioning

confidence: 99%

“…77 The two most recent revisions apply to apathy in the context of brain disorders 4 or specifically for neurocognitive disorders. 37 These aimed to achieve better adaptation for use in clinical trials and to increase the validity of apathy as a clinical construct by providing a clinical and scientific framework. While the revisions to the diagnostic criteria proposed in 2018 4 preserved the overall diagnostic structure, they included the…”

Section: Criterion Bmentioning

confidence: 99%

“…A further advancement, the 2021 Consensus Diagnostic Criteria for Apathy in Neurocognitive Disorders, were developed in collaboration with regulatory authorities and other stakeholders and apply specifically to those with a syndrome of cognitive impairment or dementia. 37 A particular goal was to facilitate use of the criteria among those with either mild or advanced cognitive deficits or physical impairment. The criteria utilize the 3-dimension construct of apathy: diminished initiative/activity, interest/enthusiasm, and emotional expression/responsiveness.…”

Section: Symptoms and Durationmentioning

confidence: 99%

“…31 Currently, no medications are approved for the treatment of apathy in NCDs. 32,33 With better understanding of the mechanistic underpinnings of apathy, 34,35 combined with ongoing efforts to refine its diagnostic criteria, 4,36,37 apathy is increasingly becoming a target for clinical trials. 32,33 Recent efforts by key opinion leaders and regulatory officials have led to diagnostic criteria for apathy specifically in neurocognitive disorders, defining it as an indication for treatment.…”

Section: Introductionmentioning

confidence: 99%

“…32,33 Recent efforts by key opinion leaders and regulatory officials have led to diagnostic criteria for apathy specifically in neurocognitive disorders, defining it as an indication for treatment. 3,37 Given the increased interest in and recognition of apathy as an important target for research and intervention, 13 this paper 1) offers a critical evaluation of recent advances in key areas of research focusing on apathy as a treatment target; 2) provides suggestions for future trial designs; and 3) identifies areas of research warranting future attention.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials

Mortby

Adler

Agüera-Ortíz

et al. 2022

The American Journal of Geriatric Psychiatry

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Section: Assessmentmentioning

confidence: 99%

Section: Criterion Bmentioning

confidence: 99%

Section: Symptoms and Durationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials

Mortby

Adler

Agüera-Ortíz

et al. 2022

The American Journal of Geriatric Psychiatry

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Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease

et al. 2021

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OBJECTIVETo measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTSThis multicenter randomized placebo-controlled clinical trial was conducted from August 2016 to July 2020 in 9 US clinics and 1 Canadian clinic specializing in dementia care. A total of 307 potential participants were screened. Of those, 52 did not pass screening and 55 were not eligible. Participants with Alzheimer disease, mild to moderate cognitive impairment, and frequent and/or severe apathy as measured by the Neuropsychiatric Inventory (NPI) were included.INTERVENTIONS Ten milligrams of methylphenidate, twice daily, vs matching placebo. MAIN OUTCOMES AND MEASURESThe coprimary outcomes included (1) change from baseline to 6 months in the NPI apathy subscale or (2) improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change. Other outcomes include safety, change in cognition, and quality of life. RESULTSOf 200 participants, 99 were assigned to methylphenidate and 101 to placebo. The median (interquartile range) age of study participants was 76 (71-81) years; 68 (34%) were female and 131 (66%) were male. A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, −1.25; 95% CI, −2.03 to −0.47; P = .002). The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01). At 6 months, the odds ratio of having an improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was 1.90 (95% CI, 0.95-3.84; P = .07). The difference in mean change from baseline to 6 months estimated using a longitudinal model was 1.43 (95% CI, 1.00-2.04; P = .048). Cognitive measures and quality of life were not significantly different between groups. Of the 17 serious adverse events that occurred during the study, none were related to the study drug. No significant differences in the safety profile were noted between treatment groups.CONCLUSIONS AND RELEVANCE This study found methylphenidate to be a safe and efficacious medication to use in the treatment of apathy in Alzheimer disease.

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Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders

Cummings,

Lanctot,

Grossberg

et al. 2024

JAMA Neurol

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ImportanceNeuropsychiatric syndromes (NPSs) are common in neurodegenerative disorders (NDDs); compromise the quality of life of patients and their care partners; and are associated with faster disease progression, earlier need for nursing home care, and poorer quality of life. Advances in translational pharmacology, clinical trial design and conduct, and understanding of the pathobiology of NDDs are bringing new therapies to clinical care.ObservationsConsensus definitions have evolved for psychosis, agitation, apathy, depression, and disinhibition in NDDs. Psychosocial interventions may reduce mild behavioral symptoms in patients with NDD, and pharmacotherapy is available for NPSs in NDDs. Brexpiprazole is approved for treatment of agitation associated with Alzheimer disease dementia, and pimavanserin is approved for treatment of delusions and hallucinations associated with psychosis of Parkinson disease. Trials are being conducted across several of the NDDs, and a variety of mechanisms of action are being assessed for their effect on NPSs.Conclusions and RelevanceDetection and characterization of NPSs in patients with NDDs is the foundation for excellent care. New definitions for NPSs in NDDs may inform choices regarding clinical trial populations and translate into clinical practice. Psychosocial and pharmacologic therapies may reduce behavioral symptoms and improve quality of life for patients and caregivers. Approved agents may establish regulatory precedents, demonstrate successful trial strategies, and provide the foundation for further advances in treatment development.

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Diagnostic criteria for apathy in neurocognitive disorders

Cited by 96 publications

References 137 publications

Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials

Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials

Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease

Progress in Pharmacologic Management of Neuropsychiatric Syndromes in Neurodegenerative Disorders

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